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Radiosensitization effect of STI-571 on pancreatic cancer cells in vitro

Authors
 HYE WON CHUNG  ;  JING WEN  ;  JONG-BAECK LIM  ;  SEUNGMIN BANG  ;  SEUNG WOO PARK  ;  SI YOUNG SONG 
Citation
 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, Vol.75(3) : 862-869, 2009 
Journal Title
 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 
ISSN
 0360-3016 
Issue Date
2009
MeSH
Analysis of Variance ; Apoptosis ; Benzamides ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor/methods ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Formazans/metabolism ; Genes, ras/genetics* ; Humans ; Imatinib Mesylate ; Mutation/genetics ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/radiotherapy* ; Phospholipase C gamma/metabolism ; Phosphorylation/drug effects ; Piperazines/therapeutic use* ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-kit/metabolism* ; Pyrimidines/therapeutic use* ; Radiation Tolerance/drug effects* ; Radiation Tolerance/genetics ; Radiation-Sensitizing Agents/therapeutic use* ; Receptor, Platelet-Derived Growth Factor beta/metabolism* ; Tetrazolium Salts/metabolism ; Thiazoles/metabolism ; Time Factors
Abstract
PURPOSE: To examine STI-571-induced radiosensitivity in human pancreatic cancer cells in vitro. METHODS AND MATERIALS: Three human pancreatic cancer cell lines (Bxpc-3, Capan-1, and MiaPaCa-2) exhibiting different expression levels of c-Kit and platelet-derived growth factor receptor beta (PDGFRbeta) and showing different K-ras mutation types were used. For evaluation of the antitumor activity of STI-571 in combination with radiation, clonogenic survival assays, Western blot analysis, and the annexin V/propidium iodide assay with microscopic evaluation by 4',6-diamidino-2-phenylindole were conducted. RESULTS: Dramatic phosphorylated (p)-c-Kit and p-PDGFRbeta attenuation, a modest dose- and time-dependent growth inhibition, and significant radiosensitization were observed after STI-571 treatment in view of apoptosis, although the levels of growth inhibition and increased radiosensitization were different according to cell lines. The grades of radiosensitivity corresponded to the attenuation levels of p-c-Kit and p-PDGFRbeta by STI-571, particularly to those of p-c-Kit, and the radiosensitivity was partially affected by K-ras mutation in pancreatic cancer cells. Among downstream pathways associated with c-Kit or PDGFRbeta, p-PLCgamma was more closely related to radiosensitivity compared with p-Akt1 or p-extracellular signal-regulated kinase 1. CONCLUSION: STI-571 enhances radiation response in pancreatic cancer cells. This effect is affected by the attenuation levels of p-c-Kit or p-PDGFRbeta, and K-ras mutation status. Among them, p-c-Kit plays more important roles in the radiosensitivity in pancreatic cancer compared with p-PDGFRbeta or K-ras mutation status.
Full Text
http://www.sciencedirect.com/science/article/pii/S0360301609009298
DOI
10.1016/j.ijrobp.2009.06.021
Appears in Collections:
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Wen, Jing(문정)
Park, Seung Woo(박승우) ORCID logo https://orcid.org/0000-0001-8230-964X
Bang, Seungmin(방승민) ORCID logo https://orcid.org/0000-0001-5209-8351
Song, Si Young(송시영) ORCID logo https://orcid.org/0000-0002-1417-4314
Lim, Jong Baeck(임종백) ORCID logo https://orcid.org/0000-0003-0419-0422
Chung, Hye Won(정혜원)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104574
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